crossing96/oncoscreening huggingface dataset:
Combining molecular and pathologic data to prognosticate non-muscle-invasive bladder cancer.	Non-muscle-invasive (NMI) bladder cancer (BC) is a chronic disease with varying oncologic outcomes requiring frequent follow-up and repeated treatments. Recurrence (in up to 80%) is the main problem for pTa NMI-BC patients, whereas progression (in up to 45%) is the main threat in pT1 and carcinoma in situ (CIS) NMI-BC. In a recent European Organization for Research and Treatment of Cancer (EORTC) analysis, multiplicity, tumor-size and prior recurrence rate are the most important variables for recurrence. Tumor grade, stage, and CIS are the most important variables for progression to muscle-invasive (MI)-BC. However, reproducibility of pathologic stage and grade is modest, which is a major concern to clinicians. Molecular markers are promising for predicting clinical outcome of NMI-BC, especially because clinicopathologic variables are not sufficient for individual prediction of prognosis. Several obstacles and opportunities have been linked to molecular markers. The role for molecular markers to predict recurrence seems limited because multifocal disease and incomplete treatment probably are more important for recurrence than the molecular features of a removed tumor. Prediction of progression with molecular markers holds considerable promise. Examples are the combination of immunohistochemical markers, gene expression signatures, and molecular grade (based on FGFR3 mutation status and Ki-67 expression). Nevertheless, the value of molecular markers over clinicopathologic indexes is still being questioned and their clinical use limited. One of the reasons may be that reproducibility of prognostic (clinical and molecular) markers in NMI-BC has been understudied.	bladder
A comparison of hexaminolevulinate (Hexvix(®)) fluorescence cystoscopy and white-light cystoscopy for detection of bladder cancer: results of the HeRo observational study.	BACKGROUND: To date, no study has presented results of photodynamic diagnosis (PDD) cystoscopy compared with white-light cystoscopy (WLC) in daily practice. The aim of the present study is to evaluate the diagnostic accuracy of hexylaminolevulinate hydrochloride (Hexvix(®)) PDD cystoscopy compared with standard WLC used in daily practice. METHODS: An observational, open-label, comparative, controlled (within patient), multicenter study was carried out on 96 consecutive patients with suspected or confirmed bladder cancer. All patients had standard WLC followed by blue-light cystoscopy (BLC). Positive lesions detected using WLC and BLC were recorded. Biopsies/resection of each positive lesion were taken after the bladder was inspected. Sensitivity, specificity, positive predictive value, and negative predictive value with each method were calculated. RESULTS: Overall, 234 suspicious lesions were detected; 108 (46.2%) were histologically confirmed to be bladder tumors/carcinoma in situ (CIS). The sensitivity of BLC biopsies was significantly higher than for WLC technique (99.1 vs 76.8%; p < 0.00001). The relative sensitivity of BLC versus WLC was 1.289, showing superiority of BLC of 28.9%. The specificity of BLC biopsies was not significantly different compared with WLC (36.5 vs 30.2%). Positive predictive value for BLC- and WLC-guided biopsies was 54.9 and 50.9%, respectively. Negative predictive value per biopsy for BLC- and WLC-guided biopsies was 97.4 and 64.8%, respectively. BLC and WLC reached the correct diagnosis in 97.9 and 88.5% of patients, respectively. This difference was statistically significant (p = 0.0265). The lack of a random biopsy protocol was the major limitation of the study. CONCLUSIONS: Hexvix(®) PDD cystoscopy used in daily practice enhances the diagnostic accuracy of standard cystoscopy with higher negative predictive value, potentially permitting an improvement in patient prognosis.	bladder
[A renal cell carcinoma with metastasis to the urinary bladder].	We report the case of a renal cell carcinoma with solitary metastasis to the urinary bladder, occurring 3 years after radical nephrectomy in a 68-year-old patient. The cystoscopy revealed a solid and rounded bladder lesion with a fine footstalk. Transurethral resection was performed and the pathological diagnosis was of eosinophil cell and clear cell carcinoma. The patient also presented secondary lesions in under- and upper-diaphragmatic lymph node area, brain and lung; therefore, he received treatment with several systemic therapies (Sorafenib, Sutent, Everolimus, IFN-alpha, Oxaliplatin and Gemcitabine).	bladder
Obesity is associated with worse oncological outcomes in patients treated with radical cystectomy.	OBJECTIVE: To investigate the association between body mass index (BMI) and oncological outcomes in patients after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) in a large multi-institutional series. PATIENTS AND METHODS: Data were collected from 4118 patients treated with RC and pelvic lymphadenectomy for UCB. Patients receiving preoperative chemotherapy or radiotherapy were excluded. Univariable and multivariable models tested the effect of BMI on disease recurrence, cancer-specific mortality and overall mortality. BMI was analysed as a continuous and categorical variable (<25 vs 25-29 vs ≥30 kg/m(2)). RESULTS: Median BMI was 28.8 kg/m(2) (interquartile range 7.9); 25.3% had a BMI <25 kg/m(2), 32.5% had a BMI between 25 and 29.9 kg/m(2), and 42.2% had a BMI ≥30 kg/m(2). Patients with a higher BMI were older (P < 0.001), had higher tumour grade (P < 0.001), and were more likely to have positive soft tissue surgical margins (P = 0.006) compared with patients with lower BMI. In multivariable analyses that adjusted for the effects of standard clinicopathological features, BMI >30 was associated with higher risk of disease recurrence (hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.46-1.91, P < 0.001), cancer-specific mortality (HR 1.43, 95% CI 1.24-1.66, P < 0.001), and overall mortality (HR 1.81, CI 1.60-2.05, P < 0.001). Themain limitation is the retrospective design of the study. CONCLUSIONS: Obesity is associated with worse cancer-specific outcomes in patients treated with RC for UCB. Focusing on patient-modifiable factors such as BMI may have significant individual and public health implications in patients with invasive UCB.	bladder
BCG-induced granulomatous prostatitis--an incidental finding on FDG PET-CT.	We present a case of granulomatous prostatitis that presented in a rare way as an incidentally discovered focus of increased FDG activity within the prostate on PET-CT in a patient who had previously undergone intravesical bacille Calmette-Guérin treatment for bladder cancer. FDG uptake is commonly discovered in organs distant from the region of primary interest on PET-CT and so it is important to be aware of the potential causes of this.	bladder
Deregulation of Rab and Rab effector genes in bladder cancer.	Growing evidence indicates that Rab GTPases, key regulators of intracellular transport in eukaryotic cells, play an important role in cancer. We analysed the deregulation at the transcriptional level of the genes encoding Rab proteins and Rab-interacting proteins in bladder cancer pathogenesis, distinguishing between the two main progression pathways so far identified in bladder cancer: the Ta pathway characterized by a high frequency of FGFR3 mutation and the carcinoma in situ pathway where no or infrequent FGFR3 mutations have been identified. A systematic literature search identified 61 genes encoding Rab proteins and 223 genes encoding Rab-interacting proteins. Transcriptomic data were obtained for normal urothelium samples and for two independent bladder cancer data sets corresponding to 152 and 75 tumors. Gene deregulation was analysed with the SAM (significant analysis of microarray) test or the binomial test. Overall, 30 genes were down-regulated, and 13 were up-regulated in the tumor samples. Five of these deregulated genes (LEPRE1, MICAL2, RAB23, STXBP1, SYTL1) were specifically deregulated in FGFR3-non-mutated muscle-invasive tumors. No gene encoding a Rab or Rab-interacting protein was found to be specifically deregulated in FGFR3-mutated tumors. Cluster analysis showed that the RAB27 gene cluster (comprising the genes encoding RAB27 and its interacting partners) was deregulated and that this deregulation was associated with both pathways of bladder cancer pathogenesis. Finally, we found that the expression of KIF20A and ZWINT was associated with that of proliferation markers and that the expression of MLPH, MYO5B, RAB11A, RAB11FIP1, RAB20 and SYTL2 was associated with that of urothelial cell differentiation markers. This systematic analysis of Rab and Rab effector gene deregulation in bladder cancer, taking relevant tumor subgroups into account, provides insight into the possible roles of Rab proteins and their effectors in bladder cancer pathogenesis. This approach is applicable to other group of genes and types of cancer.	bladder
Brachytherapy after external beam radiotherapy and limited surgery preserves bladders for patients with solitary pT1-pT3 bladder tumors.	BACKGROUND: Several French, Belgian and Dutch radiation oncologists have reported good results with the combination of limited surgery after external beam radiotherapy (EBRT) followed by brachytherapy in early-stage muscle-invasive bladder cancer. PATIENTS AND METHODS: Data from 12 of 13 departments which are using this approach have been collected retrospectively, in a multicenter database, resulting in 1040 patients: 811 males and 229 females with a median age of 66 years, range 28-92 years. Results were analyzed according to tumor stage and diameter, histology grade, age and brachytherapy technique, continuous low-dose rate (CLDR) and pulsed dose rate (PDR). RESULTS: At 1, 3 and 5 years, the local recurrence-free probability was 91%, 80% and 75%, metastasis-free probability was 91%, 80% and 74%, disease-free probability was 85%, 68% and 61% and overall survival probability was 91%, 74% and 62%, respectively. The differences in the outcome between the contributing departments were small. After multivariate analysis, the only factor influencing the local control rate was the brachytherapy technique. Toxicity consisted mainly of 24 fistula, 144 ulcers/necroses and 93 other types. CONCLUSIONS: EBRT followed by brachytherapy, combined with limited surgery, offers excellent results in terms of bladder sparing for selected groups of patients suffering from bladder cancer.	bladder
Schistosomiasis and bladder cancer: similarities and differences from urothelial cancer.	Through the years, schistosoma-associated bladder cancer was believed to be a unique entity of disease, different from urothelial cancer. As carcinogenesis is a highly complex process resulting from the accumulation of many genetic and epigenetic changes leading to alterations in the cell proliferation and regulation process, confirmation of their minute differences or similarities are extremely difficult. In bladder cancer, many of these carcinogenic cascades were not fully documented in spite of the efforts undertaken. The control of schistosomiasis and the subsequent decrease in the intensity of infestation showed feature changes approaching that of urothelial tumors. However, schistosoma-associated bladder cancer still presents in more advanced stages than schistosoma-non-associated urothelial cancer. Furthermore, many data were collected proving that, upon applying the same treatment protocol and management care, stage-by-stage comparison of the treatment end results were found to be similar in bladder cancer patients with the different etiologies.	bladder
Recurring multifocal leiomyosarcoma of the urinary bladder 22 years after therapy for bilateral (hereditary) retinoblastoma: a case report and review of the literature.	We report on a case of urinary bladder leiomyosarcoma in a 23-year-old woman, 22 years after therapy for bilateral retinoblastoma. The tumor presented with dysuria and macroscopic haematuria. Cystoscopy revealed a tumor localized in the trigonum covered by an ulcerated urothelium. The patient underwent a transvesical tumor resection. Eight months later, a second leiomyosarcoma developed in the vertex, at a site different from the previous one. A cystoscopic trans-urethral tumor resection was performed, followed by combined chemotherapy. One year later another recurrence occurred at the site of the primary resection. Open laparotomic resection of the involved bladder wall was performed. The patient remains both recurrence and metastases free after twenty months of follow-up. Molecular analysis of the peripheral blood showed rare germline point mutation in the intron 24 of the RB1 gene. FISH analysis of the tumor tissue revealed polyploid cells with relative loss of normal RB1 gene locus, indicating deletion and second hit loss of the second RB1 allele function. Along with the ten previously reported cases, this report suggests a non-random association between the hereditary retinoblastoma and urinary bladder leiomyosarcoma. Therapy with cyclophosphamide seems to be an important risk factor. Life-long surveillance for second malignancies, including bladder leiomyosarcoma is therefore mandatory in these patients.	bladder
Epithelial plasticity, cancer stem cells, and the tumor-supportive stroma in bladder carcinoma.	High recurrence rates and poor survival rates of metastatic bladder cancer emphasize the need for a drug that can prevent and/or treat bladder cancer progression and metastasis formation. Accumulating evidence suggests that cancer stem/progenitor cells are involved in tumor relapse and therapy resistance in urothelial carcinoma. These cells seem less affected by the antiproliferative therapies, as they are largely quiescent, have an increased DNA damage response, reside in difficult-to-reach, protective cancer stem cell niches and express ABC transporters that can efflux drugs from the cells. Recent studies have shown that epithelial-to-mesenchymal transition (EMT), a process in which sessile, epithelial cells switch to a motile, mesenchymal phenotype may render cancer cells with cancer stem cells properties and/or stimulate the expansion of this malignant cellular subpopulation. As cancer cells undergo EMT, invasiveness, drug resistance, angiogenesis, and metastatic ability seem to increase in parallel, thus giving rise to a more aggressive tumor type. Furthermore, the tumor microenvironment (tumor-associated stromal cells, extracellular matrix) plays a key role in tumorigenesis, tumor progression, and metastasis formation. Taken together, the secret for more effective cancer therapies might lie in developing and combining therapeutic strategies that also target cancer stem/progenitor cells and create an inhospitable microenvironment for highly malignant bladder cancer cells. This review will focus on the current concepts about the role of cancer stem cells, epithelial plasticity, and the supportive stroma in bladder carcinoma. The potential implications for the development of novel bladder cancer therapy will be discussed.	bladder
[A second transurethral resection could be not necessary in all high grade non-muscle-invasive bladder tumors].	OBJECTIVES: Evaluate the rate of residual tumor, understaging and perioperative complications in patients with high grade non-muscle-invasive bladder cancer who underwent second transurethral resection (re-TUR). MATERIAL AND METHODS: A retrospective review of 47 patients with high grade non-muscle-invasive bladder cancer who underwent second TUR from January 2007 to December 2009 at our institution. We evaluated the rate of residual tumor and understaging detected by re-TUR, complications, and the cost of the surgery. RESULTS: Twenty-two patients underwent second TUR because of the absence of muscle in the initial resection specimen (cTx). We observed residual disease in 8/47 patients (17%) and understaging in 2 cases (4.2%), the only 2 patients understaged muscularis propria was not present in the sample of initial TUR. The other 20 cTx (90%) were cT0 in the re-TUR. We did not identify any case of cT1 understaged in the re-TUR (≥cT2). Six patients (12.6%) reported complications related with the second TUR (one urethral stricture, two patients required reintervention because of bleeding, one febrile urinary infection and two bladder perforations). CONCLUSIONS: Our findings show that the absence of muscle in the initial resection specimen is the only risk factor for understaging. Therefore, we consider re-TUR is mandatory in these cases. On the other hand, when complete TUR has been performed and the muscularis propria is present and tumor free (cTa-T1), we consider systematic re-TUR is not necessary and only indicated in selected patients, even more if we consider that re-TUR is not exempt from complications.	bladder
Increased risk of bladder cancer with pioglitazone therapy in patients with diabetes: a meta-analysis.	AIMS: Emerging studies suggest a possible increased risk of bladder cancer with pioglitazone therapy. We therefore pooled data available to examine the association between pioglitazone therapy and bladder cancer in patients with diabetes. METHODS: We searched Medline and Embase to identify studies that reported the effect of pioglitazone on bladder cancer among diabetic patients. Summary effect estimates were derived using a fixed-effects meta-analysis model. RESULTS: Five studies included 2,350,908 diabetic patients. Pioglitazone was associated with a significantly higher risk of bladder cancer (relative risk [RR] 1.17, 95% confidence interval (CI) 1.03-1.32, P=0.013). No relation between pioglitazone and bladder cancer was found for duration of therapy <12 months and cumulative dose <28,000 mg. The RR for bladder cancer in subjects with 12-24 months of pioglitazone use was 1.34 (95% CI 1.08-1.66, P=0.008). The effect was even stronger for cumulative treatment duration >24 months (RR 1.38, 95% CI 1.12-1.70, P=0.003). There was a significant risk for patients with cumulative dose >28,000 mg (RR 1.58, 95% CI 1.12-2.06, P=0.001). CONCLUSIONS: Pioglitazone treatment appears to be associated with a significantly increased risk of bladder cancer in patients with diabetes.	bladder
Cystic mucinous tumors of the urachus: carcinoma in situ or adenoma of unknown malignant potential?	Mucinous cystadenocarcinomas of the urachus are rare. Mucinous benign or premalignant tumors are even rarer, yet pose a challenge in diagnosis and management. We report a case of a 66-year-old man with lower abdominal pain who had a large cystic tumor at the dome of the bladder. En-bloc resection of the tumor with partial cystectomy revealed mucinous cystadenocarcinoma in situ. We reviewed the characteristics of all seven previously reported cases. These tumors are pre-malignant and can cause significant morbidity and mortality. They need to be treated similar to conventional mucinous cystadenocarcinoma by wide surgical resection and partial cystectomy.	bladder
Integrated genomic and gene expression profiling identifies two major genomic circuits in urothelial carcinoma.	Similar to other malignancies, urothelial carcinoma (UC) is characterized by specific recurrent chromosomal aberrations and gene mutations. However, the interconnection between specific genomic alterations, and how patterns of chromosomal alterations adhere to different molecular subgroups of UC, is less clear. We applied tiling resolution array CGH to 146 cases of UC and identified a number of regions harboring recurrent focal genomic amplifications and deletions. Several potential oncogenes were included in the amplified regions, including known oncogenes like E2F3, CCND1, and CCNE1, as well as new candidate genes, such as SETDB1 (1q21), and BCL2L1 (20q11). We next combined genome profiling with global gene expression, gene mutation, and protein expression data and identified two major genomic circuits operating in urothelial carcinoma. The first circuit was characterized by FGFR3 alterations, overexpression of CCND1, and 9q and CDKN2A deletions. The second circuit was defined by E3F3 amplifications and RB1 deletions, as well as gains of 5p, deletions at PTEN and 2q36, 16q, 20q, and elevated CDKN2A levels. TP53/MDM2 alterations were common for advanced tumors within the two circuits. Our data also suggest a possible RAS/RAF circuit. The tumors with worst prognosis showed a gene expression profile that indicated a keratinized phenotype. Taken together, our integrative approach revealed at least two separate networks of genomic alterations linked to the molecular diversity seen in UC, and that these circuits may reflect distinct pathways of tumor development.	bladder
Rsf-1/HBXAP overexpression is independent of gene amplification and is associated with poor outcome in patients with urinary bladder urothelial carcinoma.	BACKGROUNDS: Urothelial carcinoma of the urinary bladder (UCUB) is prevalent in developed countries. It often shows genetic instability and is associated with amplification (or gain) of various oncogenic genes or suppressive genes. Rsf-1, a subunit of ATP-dependent chromatin-remodelling complexes that mediates ATPase-dependent chromatin remodelling, confers tumour aggressiveness in certain carcinomas. The authors evaluate the Rsf-1 gene and expression status and its associations with clinicopathological features and survival in their UCUB collection. METHODS: Immunohistochemistry was used to assess the Rsf-1 expression profile in 295 UCUB specimens, and was found to correlate with clinicopathological data. Real-time RT-PCR and fluorescence in situ hybridisation were used to detect RSF-1 mRNA expression and gene dosage in 20 independent cases. Western blot analysis was used to evaluate Rsf-1 protein expression in human urothelial cell lines. RESULTS: Rsf-1 overexpression was demonstrated in 101 cases (34.2%), and was significantly associated with advanced primary tumour (p<0.001), nodal metastasis (p=0.004), higher histological grades (p=0.001) and frequent mitoses (p<0.001). Moreover, it was predictive in disease-specific survival and metastasis-free survival in both univariate and multivariate analyses (p<0.0001 for both). Although RSF-1 gene amplification can be barely detected, its mRNA expression is significantly enhanced in tumours with higher primary tumour (p=0.041) and positive nodal statuses (p=0.010), respectively. Rsf-1 protein was abundant in invasive urothelial carcinoma cells but was not benign. CONCLUSIONS: Overexpression of Rsf-1 is associated with higher tumour stage and poorer clinical outcome. The current study by the authors suggests gene amplification-independent mechanisms driving Rsf-1 overexpression during UCUB tumour progression.	bladder